Podwyższony poziom inhibitora aktywatora plazminogenu-1 w surowicy krwi jest związany z częstością napadów, opornością na leki i markerami zapalenia mózgu u dzieci z epilepsją

BACKGROUND: Neuroinflammation and blood-brain barrier (BBB) disruption are increasingly recognized as key pathophysiological mechanisms in epilepsy. Plasminogen Activator Inhibitor-1 (PAI-1), a critical regulator of fibrinolysis and extracellular matrix remodeling, has been implicated in inflammatory processes, but its specific role in pediatric epilepsy remains largely unexplored. This study aimed to investigate the association of PAI-1 with neuroinflammation, seizure susceptibility, and clinical outcomes in a cohort of pediatric epilepsy patients. METHODS: In this case-control study, we enrolled 200 pediatric patients with epilepsy and 100 age- and sex-matched healthy controls. Serum levels of PAI-1, pro- and anti-inflammatory cytokines (including IL-6, IL-1β, TNF-α), and markers of BBB disruption and neuronal injury (S100B, NSE, GFAP) were quantified using enzyme-linked immunosorbent assays (ELISA). Comprehensive clinical data, including seizure frequency, epilepsy type, and treatment response, were collected. Statistical analyses, including -tests, ANOVA, Pearson correlation, and multivariate linear regression, were performed to assess group differences and identify predictors of seizure severity. Receiver Operating Characteristic (ROC) analysis was used to evaluate the diagnostic performance of PAI-1. RESULTS: Serum PAI-1 levels were significantly elevated in epilepsy patients compared to healthy controls (28.47 ± 12.10 ng/mL vs. 11.35 ± 5.05 ng/mL;  < 0.001). PAI-1 concentrations demonstrated a strong positive correlation with seizure frequency ( = 0.537,  < 0.001) and were significantly higher in patients with drug-resistant epilepsy ( < 0.001). ROC analysis revealed that PAI-1 is an excellent diagnostic biomarker for epilepsy (AUC = 0.916). Among all variables included in the model, PAI-1 showed the strongest independent association with monthly seizure frequency ( = 10.79, 95% CI: 8.30-13.28,  < 0.001), supporting its role as a biomarker of seizure burden rather than a standalone clinical predictor of seizure occurrence. Furthermore, PAI-1 levels were significantly correlated with markers of neuroinflammation (IL-6:  = 0.270,  < 0.001) and BBB disruption (S100B:  = 0.271,  < 0.001). Higher PAI-1 levels were also associated with poorer quality of life scores ( = -0.227,  < 0.001). CONCLUSION: PAI-1 is significantly elevated in pediatric epilepsy and is associated with seizure burden, neuroinflammatory activation, BBB disruption, drug resistance, and poorer quality of life. In this clinical setting, PAI-1 may be more useful as a risk-stratification biomarker for identifying children with higher disease burden and possible treatment resistance, rather than as a standalone tool for predicting seizure occurrence. Longitudinal studies are needed to determine whether baseline or dynamic changes in PAI-1 can predict AED response, treatment escalation, and progression toward drug-resistant epilepsy.